Thromboembolism is a crucial part of the global disease burden. It has high incidence, high mortality and disability rates, and the mechanism of occurrence and development is extremely complex. It is difficult to detect the disease in the early stage so that we have trouble with clinical prevention and treatment in general. At present, four items of blood coagulation and D-dimer have been widely used in the evaluation and auxiliary diagnosis of thromboembolism, the monitoring of effect for antithrombotic drugs and other fields. The thrombus biomarkers including thrombin-antithrombin complex (TAT), thrombomodulin (TM), tissue plasminogen activator-inhibitor complex (t-PAIC) and α2-plasmin inhibitor-plasmin complex (PIC) fill the gap of laboratory diagnosis before clinical symptoms appear in some degree. This article aims to explain the current application status of TAT, TM, t-PAIC and PIC in thromboembolism and explore their potential application value, so as to provide a reference for selecting appropriate early monitoring indicators for high-risk population of thromboembolism.
Humans ; Tissue Plasminogen Activator ; Plasminogen Inactivators ; Thrombomodulin ; Thromboembolism ; Biomarkers

Thromboembolism is a crucial part of the global disease burden. It has high incidence, high mortality and disability rates, and the mechanism of occurrence and development is extremely complex. It is difficult to detect the disease in the early stage so that we have trouble with clinical prevention and treatment in general. At present, four items of blood coagulation and D-dimer have been widely used in the evaluation and auxiliary diagnosis of thromboembolism, the monitoring of effect for antithrombotic drugs and other fields. The thrombus biomarkers including thrombin-antithrombin complex (TAT), thrombomodulin (TM), tissue plasminogen activator-inhibitor complex (t-PAIC) and α2-plasmin inhibitor-plasmin complex (PIC) fill the gap of laboratory diagnosis before clinical symptoms appear in some degree. This article aims to explain the current application status of TAT, TM, t-PAIC and PIC in thromboembolism and explore their potential application value, so as to provide a reference for selecting appropriate early monitoring indicators for high-risk population of thromboembolism.
Humans ; Tissue Plasminogen Activator ; Plasminogen Inactivators ; Thrombomodulin ; Thromboembolism ; Biomarkers

BACKGROUND: The pathologic distinction between high-grade prostate adenocarcinoma (PAC) involving the urinary bladder and high-grade urothelial carcinoma (UC) infiltrating the prostate can be difficult. However, making this distinction is clinically important because of the different treatment modalities for these two entities. METHODS: A total of 249 patient cases (PAC, 111 cases; UC, 138 cases) collected between June 1995 and July 2009 at Seoul St. Mary's Hospital were studied. An immunohistochemical evaluation of prostatic markers (prostate-specific antigen [PSA], prostate-specific membrane antigen [PSMA], prostate acid phosphatase [PAP], P501s, NKX3.1, and α-methylacyl coenzyme A racemase [AMACR]) and urothelial markers (CK34βE12, p63, thrombomodulin, S100P, and GATA binding protein 3 [GATA3]) was performed using tissue microarrays from each tumor. RESULTS: The sensitivities of prostatic markers in PAC were 100% for PSA, 83.8% for PSMA, 91.9% for PAP, 93.7% for P501s, 88.3% for NKX 3.1, and 66.7% for AMACR. However, the urothelial markers CK34βE12, p63, thrombomodulin, S100P, and GATA3 were also positive in 1.8%, 0%, 0%, 3.6%, and 0% of PAC, respectively. The sensitivities of urothelial markers in UC were 75.4% for CK34βE12, 73.9% for p63, 45.7% for thrombomodulin, 22.5% for S100P, and 84.8% for GATA3. Conversely, the prostatic markers PSA, PSMA, PAP, P501s, NKX3.1, and AMACR were also positive in 9.4%, 0.7%, 18.8%, 0.7%, 0%, and 8.7% of UCs, respectively. CONCLUSIONS: Prostatic and urothelial markers, including PSA, NKX3.1, p63, thrombomodulin, and GATA3 are very useful for differentiating PAC from UC. The optimal combination of prostatic and urothelial markers could improve the ability to differentiate PAC from UC pathologically.
Acid Phosphatase ; Adenocarcinoma ; Carrier Proteins ; Coenzyme A ; Humans ; Immunohistochemistry ; Membranes ; Prostate* ; Seoul ; Thrombomodulin ; Urinary Bladder

Animals ; Hypertension, Pulmonary ; chemically induced ; physiopathology ; Monocrotaline ; adverse effects ; Rats ; Rats, Sprague-Dawley ; Thrombomodulin ; metabolism

OBJECTIVETo observe changes in plasma thrombomodulin (TM) and D-dimer (DD) levels in neonates with sepsis, and to investigate their significance in evaluating the patients' condition and prognosis.

METHODSFifty-six neonates with sepsis were classified into extremely critical (n=13), critical (n=22) and non-critical groups (n=21) based on neonatal critical illness score (NCIS). Fasting venous blood samples were collected on admission and in the recovery phase. Plasma TM and D-dimer levels were measured using enzyme-linked immunosorbent assay and immune turbidimetry, respectively. Twenty-six healthy neonates were selected as the control group. Plasma TM and D-dimer levels were compared between groups, and the changes after treatment were determined.

RESULTSPlasma TM levels in the extremely critical, critical and non-critical groups were 25.5±6.6, 17.3±4.7 and 13.3±2.8 µg/L respectively, significantly higher than in the control group (9.8±2.7 µg/L) (P<0.01). Plasma D-dimer levels in the extremely critical and critical groups were 744±262 and 436±147 µg/L respectively, also significantly higher than in the control group (205±61 µg/L) (P<0.01). The extremely critical group had significantly higher plasma TM and DD levels than the critical group (P<0.05), and the critical group had significantly higher plasma TM and DD levels than the non-critical group (P<0.05). All patients showed significant decreases in plasma TM and DD levels in the recovery phase after treatment (P<0.01). Plasma TM and DD levels were significantly negatively correlated with NCIS (r=-0.428, P<0.01; r=-0.363, P<0.01).

CONCLUSIONSDetermination of plasma TM and DD levels may be helpful in evaluating severity and prognosis in neonates with sepsis.

Female ; Fibrin Fibrinogen Degradation Products ; analysis ; Humans ; Infant, Newborn ; Male ; Protein Multimerization ; Sepsis ; blood ; Thrombomodulin ; blood

OBJECTIVEThis study was to detect the plasma thrombomodulin (TM), D-dimer and fibrinogen in patients with multiple myeloma (MM) and to analyze their relationship with morbid state, and also to investigate the relationship of the expression of coagulation factor with the ratio of myeloma cells.

METHODSELISA was used to detect the TM level in 45 cases of MM at different stages. The plasma level of D-dimer and fibrinogen was detected by STA automatic coagulation analyser.

RESULTSThe level of plasma TM in newly diagnosed patients was higer than that in normal control group and in platform stage group (P < 0.01; P < 0.05). There were significant differences between relapsed or refractory group and normal control group or those reached platform stage group (P < 0.05). Meanwhile, the level of plasma TM in the group of thalidomide combined with chemotherapy was higer than that in newly diagnosed patients (P < 0.05). The level of plasma D-dimer and fibrinogen of MM patients was higher than that in normal controls (P < 0.01;P < 0.05). The expression of D-Dimer in relapsed or refractory group reached the maximum. Also, the level of plasma D-Dimer in group of thalidomide combined chemotherapy was higer than in newly diagnosed patients (P < 0.05). The expression of coagulation factor did not correlate with the ratio of myeloma cells.

CONCLUSIONSLevel of plasma TM, D-Dimer and fibrinogen of MM patients is higher than that in control group. The level of plasma TM and D-Dimer can be elevated when thalidomide used, which indirectly suggested the tendency for thrombosis in MM patients.

Blood Coagulation Tests ; Fibrin Fibrinogen Degradation Products ; Fibrinogen ; Humans ; Multiple Myeloma ; Thalidomide ; Thrombomodulin ; Thrombosis

BACKGROUND AND OBJECTIVES: The hyperproliferative character of human cholesteatoma epithelium was confirmed through various hyperproliferation associated antibody expressions. Among the various approaches for evaluating proliferative activity, thrombomodulin (TM) is a cell surface glycoprotein which forms a high affinity non-covalent complex with thrombin and is a differentiation marker for spinous layer keratinocytes. Several animal models have been introduced to study cholesteatoma pathogenesis, among which canal ligation model using Mongolian gerbils is of much interest, because it can potentially provide information on cell differentiation and proliferation of cholesteatoma. In this study, we investigated the hyperproliferative characteristics of canal ligation cholesteatoma by comparing deep meatal skin and retroauricular skin. Another purpose of this study was to provide the morphological basis for further animal studies concerning cholesteatoma pathogenesis. MATERIALS AND METHOD: Using immunohistochemical technique with anti-monoclonal antibody, we investigated TM expression in the canal ligation cholesteatoma, deep meatal skin and retroauricular skin of Mongolian gerbil. RESULTS: Experimental cholesteatoma induced by canal ligation and deep meatal skin showed TM expression especially in the suprabasal layers. TM expression of experimental cholesteatoma is much more intense than that of deep meatal skin. CONCLUSION: Experimental cholesteatoma revealed an altered differentiation in suprabasal layer, suggesting that this animal model can be used for further study in the epithelial differentiation and proliferation of cholesteatoma.
Animals ; Cell Differentiation ; Cholesteatoma* ; Epithelium ; Gerbillinae ; Humans ; Keratinocytes ; Ligation ; Membrane Glycoproteins ; Models, Animal ; Skin ; Thrombin ; Thrombomodulin*

BACKGROUND/AIMS: Recently, recombinant human soluble thrombomodulin (rTM) has been developed as a new drug for disseminated intravascular coagulation (DIC). This study aims to evaluate the clinical benefit of rTM in patients with sepsis-induced DIC caused by acute cholangitis who underwent biliary drainage. METHODS: Patients were divided into two groups: the rTM therapy group and the non-rTM therapy group. The primary outcome was the DIC resolution rate at 7 days, and the secondary outcome was 28-day mortality rate. RESULTS: Thirty-five patients were treated by rTM, and 36 patients were treated without rTM for DIC. The rate of resolution of DIC at day 7 was significantly higher in the rTM group than in the non-rTM group (82.9% vs 55.6%, p=0.0012). Compared with the non-rTM group, the 28-day survival rate of the r-TM group was significantly higher (rTM vs non-rTM, 91.4% vs 69.4%, p=0.014). According to multivariate analysis, non-rTM (hazard ratio [HR], 2.681) and CRP (HR, 2.370) were factors related to decreased survival. CONCLUSIONS: rTM treatment may have a positive impact on improving DIC and survival rates in patients with severe acute cholangitis.
Cholangitis* ; Dacarbazine ; Disseminated Intravascular Coagulation* ; Drainage ; Humans ; Mortality ; Multivariate Analysis ; Survival Rate ; Thrombomodulin* ; Thrombosis

Mature cystic teratoma (MCT) is one of the most common benign ovarian tumors, but 1-2% of MCTs are transformed to a malignant neoplasm. Urothelial carcinoma (UC) or transitional cell carcinoma is the most common cancer in the urinary tract. However, UC is a very rare component of transformed malignancy of MCT. Here we report a case of UC arising in an MCT in a 52-year-old woman. Grossly, the ovary was partly cystic and partly solid. Microscopically, the cyst revealed the classic features of MCT and the solid area was papillary UC. By immunohistochemistry using cytokeratins and thrombomodulin, the UC showed a similar expression to that of UC arising in the urinary tract, rather than resembling a primary transitional cell carcinoma of the ovary. When UC is found in a component of MCT, the origin of the carcinoma should be evaluated and urinary tract examinations are required to rule out metastasis.
Carcinoma, Transitional Cell ; Female ; Humans ; Immunohistochemistry ; Keratins ; Middle Aged ; Neoplasm Metastasis ; Ovarian Neoplasms ; Ovary ; Teratoma ; Thrombomodulin ; Urinary Tract

Despite abundant blood supply, metastatic tumors of the penis are rare. We report herein a case of metastatic cancer of the penis from urinary bladder carcinoma in a 80-year-old man. He presented with 1 month history of erythematous tender mass on the penis which developed 16 months later after the diagnosis of carcinoma of the urinary bladder had been made. Skin biopsy from this lesion revealed variable sized atypical cells with hyperchromatic and pleomorphic nuclei similar to those of the urinary bladder. On immunohistochemical staining, infiltrating cells of both bladder and penis showed positive reaction to thrombomodulin and carcinoembryonic antigen(CEA), but negative reaction to cytokeratin20 and C-erB-2 oncogene.
Aged, 80 and over ; Biopsy ; Diagnosis ; Humans ; Male ; Neoplasm Metastasis ; Oncogenes ; Penile Neoplasms* ; Penis ; Skin ; Thrombomodulin ; Urinary Bladder*